title: Lipopeptide Laur-CKK-NH2 dimer preserves daptomycin susceptibility and enhances its activity against Enterococcus faecalis.
abstract: OBJECTIVE
  An experimental study was performed to evaluate both in vitro and in vivo the kind of interaction between the Laur-CKK-NH2 dimer and daptomycin using two Enterococcus faecalis strains with different patterns of susceptibilities.
  
  
  METHODS
  We evaluated whether selection for daptomycin-resistant E. faecalis could be prevented in vitro by combining daptomycin with the Laur-CKK-NH2 dimer. The strains were serially exposed in broth to 2-fold stepwise increasing concentrations of daptomycin alone or in combination with a fixed concentration (0.25×MIC) of the Laur-CKK-NH2 dimer. We also performed an in vitro synergy study. For in vivo studies, a mouse model of enterococcal sepsis was used.
  
  
  RESULTS
  In vitro experiments: exposure to daptomycin alone gradually selected for enterococci with increased MICs; and the Laur-CKK-NH2 dimer showed a positive interaction with daptomycin and was able to prevent the resistance. In vivo experiments: the main outcome measures were lethality and quantitative blood cultures; and the Laur-CKK-NH2 dimer combined with daptomycin exhibited the highest efficacy for all main outcome measurements.
  
  
  CONCLUSIONS
  These results highlight the potential usefulness of combining daptomycin with the Laur-CKK-NH2 dimer. The combination provides a future therapeutic alternative for the treatment of enterococcal severe infections.
authors.affiliation: Clinic of Infectious Diseases, Università Politecnica delle Marche-Ospedali Riuniti, Ancona, Italy. anconacmi@interfree.it
authors.forename: Oscar
authors.initials: O
authors.lastname: Cirioni
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kamysz
authors.forename: Roberto
authors.initials: R
authors.lastname: Ghiselli
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kamysz
authors.forename: Carmela
authors.initials: C
authors.lastname: Silvestri
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Orlando
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Rimini
authors.forename: Lucia
authors.initials: L
authors.lastname: Brescini
authors.forename: Eleonora
authors.initials: E
authors.lastname: Gabrielli
authors.forename: Elisa
authors.initials: E
authors.lastname: Marchionni
authors.forename: Marco
authors.initials: M
authors.lastname: Rocchi
authors.forename: Mauro
authors.initials: M
authors.lastname: Provinciali
authors.forename: Mario
authors.initials: M
authors.lastname: Guerrieri
authors.forename: Andrea
authors.initials: A
authors.lastname: Giacometti
mesh_terms: D000818:Animals; D017576:Daptomycin / Q000008:administration & dosage* / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D013293:Enterococcus faecalis / Q000187:drug effects*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D055666:Lipopeptides / Q000008:administration & dosage* / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D016896:Treatment Outcome
chemical_list: D055666:Lipopeptides; D017576:Daptomycin